Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs.

BACKGROUND: Iron deposition and ferroptosis are involved in ischemic stroke injury, but the choice of drugs for treatment is limited. PURPOSE: To investigate the potential neuroprotective effects of Rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on ischemic stroke. METHODS: Wild-type (WT) and TfR1EC cKO (specific knockout of the TfR1 gene in BMECs) mice used to establish a dMCAO model, with simultaneous administration of RosA-LIP (20 mg/kg/d, i.p.) or RosA (20 mg/kg/d, i.p.). RESULTS: The successful synthesis of RosA-LIP resulted in enhanced stability and precise delivery in both the serum and brain. The administration of RosA-LIP effectively mitigated ischemia-induced behavioral abnormalities and pathological damage. RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation. RosA-LIP effectively improved blood‒brain barrier (BBB) permeability, increased tight junctions (TJs) protein expression and reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels. Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO. CONCLUSION: RosA-LIP effectively increased the brain level of RosA and protected against ferroptosis through the regulation of TfR1 in BMECs.

Circular RNA circPHF16 enhances IL-17A expression and secretion by sequestering miR-378a-3p to activate the IL6ST axis in Graves' disease.

Interleukin-17A (IL-17A) plays a pivotal role in the pathogenesis of Graves' disease (GD), an autoimmune disorder affecting thyroid function, but the detailed regulatory mechanisms remain elusive. Circular RNAs (circRNAs) have emerged as key regulators of IL-17A expression and secretion in autoimmune diseases, yet their specific role in GD, especially within CD4 + T lymphocytes, are not well understood. In this study, a circRNA, circPHF16 (hsa_circ_0090364) was found to be highly expressed in the peripheral blood mononuclear cells and serum of GD patients. In vitro experiments in Jurkat T cells revealed that silencing of circPHF16 suppressed IL-17A expression and secretion, while overexpression of circPHF16 had the opposite effect. Furthermore, bioinformatics analysis demonstrated a circPHF16/miR-378a-3p/IL6ST pathway, in which circPHF16 regulates IL6ST expression, which, in turn, influences IL-17A expression and secretion by interacting with miR-378a-3p. In vivo studies in a mouse model of GD showed similar trends in molecular expression levels, consistent with competitive endogenous RNA interactions. Together the results of the study identify circPHF16 as a potential target in the development of new strategies for GD diagnosis and treatment, and thus, offer a theoretical foundation for clinical therapeutic approaches in GD.

Accurate Prediction of the Magnetic Ordering Temperature of Ultralow-Temperature Magnetic Refrigerants.

Adiabatic demagnetization refrigeration is known to be the only cryogenic refrigeration technology that can achieve ultralow temperatures (≪1 K) at gravity-free conditions. The key indexes to evaluate the performance of magnetic refrigerants are their magnetic entropy changes (-ΔSm) and magnetic ordering temperature (T0). Although, based on the factors affecting the -ΔSm of magnetic refrigerants, one has been able to judge if a magnetic refrigerant has a large -ΔSm, how to accurately predict their T0 remains a huge challenge due to the fact that the T0 of magnetic refrigerants is related to not only magnetic exchange but also single-ion anisotropy and magnetic dipole interaction. Here, we, taking GdCO3F (1), Gd(HCOO)F2, Gd2(SO4)3·8H2O, GdF3, Gd(HCOO)3 and Gd(OH)3 as examples, demonstrate that the T0 of magnetic refrigerants with very weak magnetic interactions and small anisotropy can be accurately predicted by integrating mean-field approximation with quantum Monte Carlo simulations, providing an effective method for predicting the T0 of ultralow-temperature magnetic refrigerants. Thus, the present work lays a solid foundation for the rational design and preparation of ultralow-temperature magnetic refrigerants in the future.

Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

Guanxin V Relieves Ventricular Remodeling by Inhibiting Inflammation: Implication from Virtual Screening, Systematic Pharmacology, Molecular Docking, and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To reveal the anti-inflammatory mechanism of Guanxin V, which is prescribed for ventricular remodeling in clinical practice.@*METHODS@#Guanxin V-, ventricular remodeling-, and inflammation-related targets were obtained through an integrated strategy of virtual screening and systematic pharmacology, and then the shared targets were visualised with a Venn diagram. Guanxin V network and the protein-protein interaction network were drawn, and enrichment analysis was conducted. Finally, the main results obtained from the integrated strategy were validated by molecular docking and in vivo experiments.@*RESULTS@#A total of 251, 11,425, and 15,246 Guanxin V-, ventricular remodeling-, and inflammation-related targets were acquired, respectively. Then, 211 shared targets were considered to contribute to the mechanism of ventricular remodeling treated by Guanxin V. Guanxin network and the protein-protein interaction network were drawn, and enrichment analysis showed some cardiovascular-related biological processes and signaling pathways. Molecular docking revealed that the Guanxin V-derived compounds could align with key targets. Final in vivo experiments proved that Guanxin V reverses ventricular remodeling by inhibiting inflammation.@*CONCLUSION@#Guanxin V relieves ventricular remodeling by regulating inflammation, which provides new ideas for the anti-ventricular remodeling mechanism of Guanxin V.

Predictive value of different critical values of slow gait speed on adverse outcomes in elderly maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To explore the predictive value of different critical values of slow gait speed on adverse outcomes in elderly maintenance hemodialysis (MHD) patients.Methods:The study was a prospective cohort study. The clinical data of elderly patients (≥ 60 years old) who received MHD treatment in the Third Affiliated Hospital of Guangzhou Medical University from March 1 to June 30, 2021 were collected, including demographic characteristics, diseases-related data and laboratory examination results. The follow-up period was one year. The six-meter walking test was used to measure the gait speed (m/s), and 0.6 m/s, 0.8 m/s and 1.0 m/s were used as the different critical values of the gait speed for grouping. The differences of clinical data between different groups were compared. Logistic regression analysis method was used to assess the association of slow gait speed with adverse outcomes (falls and hospitalization) in elderly MHD patients. The receiver operating characteristic (ROC) curve was performed to evaluate the best critical value of slow gait speed to predict the risk of falls and hospitalization.Results:A total of 108 elderly patients with MHD were included, with 57 males and 51 females. There were 43 patients (39.8%) of falls and 34 patients (31.5%) of hospitalization. There were statistically significant differences in age, Charlson's comorbidity index, and the proportions of hypertension, family support needed in daily life, walking aids needed, falls and hospitalization events among the four groups of the patients grouped according to gait speed (all P < 0.05). Multivariate logistic regression analysis results showed that the risk of falls predicted by gait speed of 0.6- < 0.8 m/s was higher than that by gait speed of > 1.0 m/s ( OR=3.973, 95% CI 1.116-14.136, P=0.033). The risk of hospitalization predicted by gait speed < 0.6 m/s was higher than that by gait speed > 1.0 m/s ( OR=9.147, 95% CI 1.658-50.453, P=0.011). The logistic regression analysis was performed with the critical values of 0.6 m/s, 0.8 m/s and 1.0 m/s as the classification variables, and the results showed that the gait speed of < 0.8 m/s was an influencing factor of the falls risk in elderly MHD patients (≥ 0.8 m/s as reference, OR=3.200, 95% CI 1.099-9.318, P=0.033). The gait speed < 0.8 m/s and < 0.6 m/s were influencing factors of hospitalization (≥ 0.8 m/s as reference, OR=3.899, 95% CI 1.355-11.216, P=0.012; ≥ 0.6 m/s as reference, OR=4.226, 95% CI 1.107-16.140, P=0.035). The area under the ROC curve for gait speed of < 0.6 m/s, < 0.8 m/s and < 1.0 m/s to predict the risk of falls were 0.605(95% CI 0.493-0.717, P=0.065), 0.668(95% CI 0.562-0.774, P=0.003), and 0.634 (95% CI 0.529-0.739, P=0.019), respectively. The best critical value of slow gait speed to predict the risk of fall was 0.73 m/s, and the area under the ROC curve was 0.720(95% CI 0.623-0.817, P < 0.001), with the sensitivity and specificity of 0.846 and 0.512, respectively. The area under the ROC curve for gait speed of < 0.6 m/s, < 0.8 m/s and < 1.0 m/s to predict the risk of hospitalization were 0.629(95% CI 0.509-0.749, P=0.032),0.683(95% CI 0.573-0.793, P=0.002), and 0.608(95% CI 0.497- 0.719, P=0.073). The best critical value of slow gait speed to predict the risk of hospitalization was 0.81 m/s, and the area under the ROC curve was 0.688(95% CI 0.576-0.800, P=0.002), with the sensitivity and specificity of 0.689 and 0.676, respectively. Conclusion:The critical value of gait speed 0.8 m/s can be used to predict the risk of falls and hospitalization in elderly MHD patients.

Psychological effect of physical function dependence on maintenance hemodialysis patients and their primary family caregivers / 中华肾脏病杂志

Objective:To investigate the psychological effect of physical function dependence on maintenance hemodialysis (MHD) patients and their primary family caregivers.Methods:The study was a cross-sectional survey. The MHD patients in the hemodialysis centre, the Third Affiliated Hospital of Guangzhou Medical University from March 2022 to June 2022 were enrolled. The patients' demographics and laboratory data were collected. Katz and Lawton-Brody questionnaires were used to assess patients' physical function, and Five Item Mental Health Inventory (MHI-5) was used to evaluate the psychological conditions of the patients and their primary family caregivers. Multiple linear regression analysis was used to analyze the influencing factors of MHI-5 scores of the patients and their primary family caregivers.Results:A total of 116 patients were included, with 61 males and 55 females. There were 47 patients (40.5%) with physical function dependence. In the physical function dependence group, serum albumin ( t=-2.512, P=0.013), MHI-5 scores of patients and their primary family caregivers ( t=-8.461, P < 0.001; t=-8.533, P < 0.001) and male ratio ( χ2=8.467, P=0.002) were significantly lower, and the age ( t=9.754, P < 0.001) and the proportions of hypertension ( χ2=20.421, P < 0.001), diabetes ( χ2=10.470, P=0.002), cardiovascular and cerebrovascular diseases ( χ2=9.898, P=0.003) were significantly higher than those in the normal physical function group. The incidence of mental disorders in MHD patients was 39.7%(46/116), and the incidence of mental disorders in the physical function dependence group was significantly higher than that in the normal physical function group [72.3%(34/47) vs. 17.4%(12/69), χ2=35.275, P < 0.001]. The incidence of mental disorders in the primary family caregivers was 32.8%(38/116), and the incidence of mental disorders in the primary family caregivers of physical function dependence group was significantly higher than that in the normal physical function group [66.0%(31/47) vs. 10.1%(7/69), χ2=39.536, P < 0.001]. The incidence of mental disorders in the primary family caregivers of MHD patients who were not spouses was significantly higher than that of spouses [46.0%(29/63) vs. 17.0%(9/53), χ2=11.028, P=0.001], and in physical function dependence group, the incidence of mental disorders in non-spouses was significantly higher than that in spouses [80.6%(25/31) vs. 37.5%(6/16), χ2=8.749, P=0.003]. Multiple linear analysis showed that bathing ( β=-5.182, P=0.015), doing laundry ( β=-7.053, P < 0.001), taking medication ( β=-8.680, P=0.003), and female patients ( β=-2.982, P=0.030) were the influencing factors of MHI-5 scores decline in MHD patients. Bathing ( β=-4.404, P=0.032), preparing meals ( β=-3.954, P=0.041), managing money ( β=-5.067, P=0.021), and female patients ( β=-2.466, P=0.042) were the influencing factors of MHI-5 scores decline in primary family caregivers. Conclusions:The incidence of physical function dependence in MHD patients is high, and its manifestations and influencing factors are diverse. The incidence of mental disorders in MHD patients and their primary family caregivers is also high, especially in patients with physical function dependence and non- spouse family caregivers. Clinicians should pay attention to and assess the physical function dependence of MHD patients as early as possible, and intervene in time. At the same time, they should also pay attention to the mental health of MHD patients and their primary family caregivers.

Effects of thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point on lumbodorsal myofascial pain syndrome of cold-damp stagnation type / 中国基层医药

Objective:To investigate the clinical efficacy of thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point on lumbodorsal myofascial pain syndrome of cold-damp stagnation type.Methods:A total of 90 patients with lumbodorsal myofascial pain syndrome of cold-damp stagnation type admitted to Zhejiang Provincial Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to April 2022 were included in this study. They were randomly divided into three groups ( n = 30/group) using the random number table method. Patients in the Chinese herbal ointment group were treated by external application of Chinese herbal ointment at the trigger point. Patients in the thunder-fire moxibustion group were treated with thunder-fire moxibustion. Patients in the combined therapy group were treated with thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point. All patients were treated for 28 consecutive days. Clinical efficacy was compared among the three groups. Before and after treatment, the Visual Analogue Scale score, local tenderness score, Oswestry Disability Index score and Pittsburgh Sleep Quality Index score were compared among the three groups. Results:Total response rate (96.67%) in the combined therapy group was significantly higher than 73.33% in the thunder-fire moxibustion group and 66.67% in the Chinese herbal ointment group ( χ2 = 9.01, 4.70, both P < 0.05). Visual Analogue Scale score and local tenderness score in the combined therapy group were (1.96 ± 0.93) points and (1.00 ± 0.69) points, respectively, which were significantly lower than (2.43 ± 0.87) points and (1.37 ± 0.56) points in the thunder-fire moxibustion group and (2.77 ± 0.86) points and (1.50 ± 0.57) points in the Chinese herbal ointment group ( F = 6.22, 5.38, both P < 0.05). The Oswestry Disability Index score in the combined therapy group was (19.80 ± 3.80) points, which was significantly lower than (22.30 ± 2.82) points in the thunder-fire moxibustion group and (23.60 ± 3.71) points in the Chinese herbal ointment group ( F = 9.07, both P < 0.05). After treatment, the Pittsburgh Sleep Quality Index score in the combined therapy group was (5.30 ± 1.12) points, which was significantly lower than (6.50 ± 1.33) points in the thunder-fire moxibustion group and (6.73 ± 1.41) points in the Chinese herbal ointment group ( F = 10.59, both P < 0.05). Conclusion:Thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point is highly effective on lumbodorsal myofascial pain syndrome of cold-damp stagnation type than monotherapy. The combined therapy can markedly reduce pain and greatly improve lumbodorsal function and sleep quality.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Progress in perioperative management of ABO-incompatible pediatric liver transplantation / 中华外科杂志

ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.

Modeling Methods and Influencing Factors for Age Estimation Based on DNA Methylation / 法医学杂志

Age estimation based on tissues or body fluids is an important task in forensic science. The changes of DNA methylation status with age have certain rules, which can be used to estimate the age of the individuals. Therefore, it is of great significance to discover specific DNA methylation sites and develop new age estimation models. At present, statistical models for age estimation have been developed based on the rule that DNA methylation status changes with age. The commonly used models include multiple linear regression model, multiple quantile regression model, support vector machine model, artificial neural network model, random forest model, etc. In addition, there are many factors that affect the level of DNA methylation, such as the tissue specificity of methylation. This paper reviews these modeling methods and influencing factors for age estimation based on DNA methylation, with a view to provide reference for the establishment of age estimation models.

A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome / 医学前沿

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

Clinical features and genetic analysis of a patient with type 2 neurofibromatosis manifested as oculomotor nerve palsy / 中华医学遗传学杂志

OBJECTIVE@#To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis.@*METHODS@#A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

Psychological effect of physical function dependence on maintenance hemodialysis patients and their primary family caregivers / 中华肝脏病杂志

Objective: To investigate the psychological effect of physical function dependence on maintenance hemodialysis (MHD) patients and their primary family caregivers. Methods: The study was a cross-sectional survey. The MHD patients in the hemodialysis centre, the Third Affiliated Hospital of Guangzhou Medical University from March 2022 to June 2022 were enrolled. The patients' demographics and laboratory data were collected. Katz and Lawton-Brody questionnaires were used to assess patients' physical function, and Five Item Mental Health Inventory (MHI-5) was used to evaluate the psychological conditions of the patients and their primary family caregivers. Multiple linear regression analysis was used to analyze the influencing factors of MHI-5 scores of the patients and their primary family caregivers. Results: A total of 116 patients were included, with 61 males and 55 females. There were 47 patients (40.5%) with physical function dependence. In the physical function dependence group, serum albumin (t=-2.512, P=0.013), MHI-5 scores of patients and their primary family caregivers (t=-8.461, P < 0.001; t=-8.533, P < 0.001) and male ratio (χ2=8.467, P=0.002) were significantly lower, and the age (t=9.754, P < 0.001) and the proportions of hypertension (χ2=20.421, P < 0.001), diabetes (χ2=10.470, P=0.002), cardiovascular and cerebrovascular diseases (χ2=9.898, P=0.003) were significantly higher than those in the normal physical function group. The incidence of mental disorders in MHD patients was 39.7%(46/116), and the incidence of mental disorders in the physical function dependence group was significantly higher than that in the normal physical function group [72.3%(34/47) vs. 17.4%(12/69), χ2=35.275, P < 0.001]. The incidence of mental disorders in the primary family caregivers was 32.8%(38/116), and the incidence of mental disorders in the primary family caregivers of physical function dependence group was significantly higher than that in the normal physical function group [66.0%(31/47) vs. 10.1%(7/69), χ2=39.536, P < 0.001]. The incidence of mental disorders in the primary family caregivers of MHD patients who were not spouses was significantly higher than that of spouses [46.0%(29/63) vs. 17.0%(9/53), χ2=11.028, P=0.001], and in physical function dependence group, the incidence of mental disorders in non-spouses was significantly higher than that in spouses [80.6%(25/31) vs. 37.5%(6/16), χ2=8.749, P=0.003]. Multiple linear analysis showed that bathing (β=-5.182, P=0.015), doing laundry (β=-7.053, P < 0.001), taking medication (β=-8.680, P=0.003), and female patients (β=-2.982, P=0.030) were the influencing factors of MHI-5 scores decline in MHD patients. Bathing (β=-4.404, P=0.032), preparing meals (β=-3.954, P=0.041), managing money (β=-5.067, P=0.021), and female patients (β=-2.466, P=0.042) were the influencing factors of MHI-5 scores decline in primary family caregivers. Conclusions: The incidence of physical function dependence in MHD patients is high, and its manifestations and influencing factors are diverse. The incidence of mental disorders in MHD patients and their primary family caregivers is also high, especially in patients with physical function dependence and non- spouse family caregivers. Clinicians should pay attention to and assess the physical function dependence of MHD patients as early as possible, and intervene in time. At the same time, they should also pay attention to the mental health of MHD patients and their primary family caregivers.

The Spectral Response of the Dual Microdisk Resonator Based on BaTiO3 Resistive Random Access Memory.

With the resistive random access memory (ReRAM) devices based on the Al/BaTiO3 (BTO)/ITO structure fabricated at hand, by cross-analyzing the resistive memory characteristics in terms of various barium titanate (BTO) film thicknesses, it is found that the device with 60 nm thick BTO can be switched more than 425 times, while the corresponding SET/RESET voltage, the on-off ratio, and the retention time are -0.69 V/0.475 V, 102, and more than 104 seconds, respectively. Furthermore, the aforementioned ReRAM with a low switching voltage and low power consumption is further integrated with a waveguide resonator in the form of a dual microdisk aligned in a parallel fashion. As the separation gap between the two microdisks is fixed at 15 µm, the ReRAM-mediated dual disk resonator would render a 180° phase reversal between the spectral outputs of the through-port and drop-port. If the gap is shortened to 10 and 5 µm, the expected phase reversal could also be retrieved due to the selective combinations of different memory states associated with each of the two ReRAM microdisks as witnessed by a series of characterization measurements.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study.

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. RESULTS: A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992-1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307-9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974-60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022-1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806-36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

Bidirectional Coupler Study for Chip-Based Spectral-Domain Optical Coherence Tomography.

A chip-based spectral-domain optical coherence tomography (SD-OCT) system consists of a broadband source, interferometer, and spectrometer. The optical power divider flatness in the interferometer's wavelength is crucial to higher signal-to-noise ratios. A Mach-Zehnder directional coupler (MZDC) structure could be utilized to smoothly maximize the splitting ratio of 50:50 on a silicon platform, with a sub-micrometer of decoupler optical path difference insensitive to the process variation up to 20 nanometers. However, the optical signal reflected from the reference and sample will go back to the same interferometer MZDC. The so-called bidirectional coupler MZDC will not illustrate a flat optical power response in the operating wavelength range but could still demonstrate at least 20 dB signal-to-noise ratio improvement in OCT after the echelle grating spectrum compensation is applied. For maintaining the axial resolution and sensitivity, the echelle grating is also insensitive to process shifts such as MZDC and could be further utilized to compensate a 3 dB bidirectional MZDC structure for a broad and flat 100 nm wavelength response in the interferometer-based on-chip SD-OCT.

Study on Leading Demonstration Effect of College Students’ Behavior in Public Health Emergencies / 中国医学伦理学

In recent years, society has gradually shifted from a "fearful" approach of unscientific plan design, unbalanced resource protection and inadequate management experience leading to the spread of public panic and negative emotions to a "comfortable" approach of proactive prevention, precise control, information symmetry, scientific response and systematic treatment in the face of public health emergencies. College students are increasingly becoming the "key minority" to participate in crisis management. This is mainly due to their values in line with social ideals, their mobility in line with disciplinary practice and volunteerism, their knowledge accumulation in multi-disciplinary cross-fertilization, and their good cognitive thinking literacy, high information media literacy and perfect social support system. Therefore, this group has a strong comprehensive advantage in public health emergencies. Based on this background, combined with on-site investigation and interview feedback, this paper considered that this group can play an active role in normal prevention and early warning beforehand, information transmission and communication at the moment the event occur, corrective cognitive implementation and disposal in the event, and scientific research innovation and popularization afterwards, so as to better play an increasingly important leading demonstration effect in public health emergencies. At the same time, it can also encourage universities to take the initiative in the process of talent training to teach people according to the concept of "change according to the matter, advance according to the time and new according to the situation", and lead college students of different majors to maximize the pioneering effect of role models in public health emergencies.

Analysis of risk factors for hemorrhage in patients with acute poisoning treated with hemoperfusion / 中华劳动卫生职业病杂志

Objective: To explore the clinical characterist ics and risk factors of hemorrhage complicated by hemoperfusion therapy in patients with acute poisoning. Methods: In January 2021, the clinical data of 196 patients with acute poisoning who received hemoperfusion therapy in the Second Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2020 were analyzed, and the patients were divided into bleeding group and non-bleeding group according to whether the patients were complicated with bleeding. Multivariate logistic regression was used to analyze the independent risk factors for hemorrhage in patients treated with hemoperfusion. Results: A total of 21 patients in the bleeding group and 175 patients in the non-bleeding group were included. There was no significant difference in general data such as gender, age, and body mass index between the two groups (P>0.05) . Organophosphorus pesticides (χ(2)= 4.56, P=0.030) , HA230 perfusion device (χ(2)=4.12, P=0.042) , platelet count (t=-2.33, P=0.009) and activated partial thromboplastin time (t=14.53, P<0.001) at 2 h of perfusion were the influencing factors of hemorrhage in patients with acute poisoning treated with hemoperfusion. Among them, organophosphorus pesticides, 2 h perfusion activated partial thromboplastin time ≥35 s and other factors were independent risk factors forcomplicated bleeding (P<0.05) . Conclusion: Patients with acute poisoning, especially organophosphorus pesticide poisoning, are at greater risk of bleeding during hemoperfusion therapy. Monitoring of changes in activated partial thromboplastin time should be strengthened and the dose of anticoagulants should be adjusted in time to reduce the risk of bleeding.